a. Field of the Invention
This invention relates to phenoxyisobutyric acid salts having valuable pharmaceutical properties, to processes for preparing said salts, to pharmaceutical preparations thereof and to a method for using said salts.
B. Prior Art
The association of excessive plasma concentrations of lipoproteins or of plasma lipids with increased risk of heart attack, stroke, and sudden death is well established. Consequently, the consensus of informed opinion is that elevated levels of cholesterol and/or triglycerides should be reduced by appropriate long term therapy.
The generally accepted Frederickson-Levy-Lees classification of lipid disorders based on lipoprotein disturbances lists five catagories, Types I to V, of hyperlipoproteinemia. This classification allows a more rational choice of therapeutic programs for the treatment of hyperlipoproteinemia, see R. I. Levy, Fed. Proc. 30, 829 (1971). Although a variety of drugs are available for the treatment of hyperlipoproteinemia, none of them is adequate for the general treatment of all types of hyperlipoproteinemias. At the present time, the preferred drugs for treating hyperlipoproteinemia are dependent on the classification of the syndrome and are thus specific for each syndrome; for example, see R. S. Lees and D. E. Wilson, New Engl. J. Med., 284, 186 (1971). The phenoxyisobutyric acid salts of this invention have been found to be effective for reducing levels of cholesterol and triglycerides in the blood of mammals exhibiting hyperlipoproteinemia and associated conditions. The acid salts are effective at dosages which do not elicit undesirable side effects. Furthermore, the salts are effective for treating hyperlipoproteinemia in general, notably the syndromes comprising hyperlipoproteinemias of Types IIa, IIb, III and IV.
The phenoxyisobutyric acid salts are prepared by a convenient process from readily available starting materials. Consequently, the salts are inexpensive and readily available.
The phenoxyisobutyric acid salts feature a combination of chemical subunits; namely, a pyridylmethyl ester of an amino acid associated with a phenoxyisobutyric acid. Related prior art compounds include 3-pyridylmethyl esters of phenoxyalkanoic acid, U.S. Pat. No. 3,369,025, issued Feb. 13, 1968 and N-(carboxyalkyl)-phenoxyalkanoic acid amides, U.S. Pat. No. 3,364,249, issued Jan. 16, 1968. These prior art compounds are distinguished from the compounds of the present invention in that they are not salts, and moreover they lack one of the chemical subunits (i.e., an amino acid residue or a pyridylmethyloxy residue) of the compounds of this invention. Additional prior art compounds are chlorophenoxyisobutyric acid salts in which the base is a 2-aminoethanol ester or derivative thereof of nicotinic acid, see U.S. Pat. No. 3,717,649, Feb. 20, 1973, and Swiss Pat. No. 513,166, Nov. 15, 1971. The latter compounds lack the amino acid residue of the compounds of this invention.